Personalized genomics inflection point

One of the world’s fastest accelerating technologies is that of genomic sequencing. The first whole human genome (6 billion base pairs) was sequenced at a cost of $3b and was completed in 2003. The current cost is $20,000 for researchers (Complete Genomics) and $48,000 for consumers (with Illumina’s EveryGenome program). Leading third-generation sequencing company Pacific Biosciences affirmed at the Cold Spring Harbor Laboratory Personal Genomes meeting September 14-17, 2009 that the company has 12 prototype instruments in operation and continues to be on track for ~$100 (“the cost of a nice dinner”) whole human genome sequencing to be commercially available in the second half of 2010. NimbleGen indicated that they may have a $2,000 exome sequencer available in 2010.

In a challenging venture capital climate, Pacific Biosciences was able to close an additional $68m round in financing on August 12, 2009. Leading commercial sequencer Complete Genomics was also notable in closing a $45m D round on August 24, 2009. The company has sequenced 14 whole human genomes to date, and hopes to sequence exponentially more, 10,000, in 2010 at a minimum cost of $5,000 per genome.

Viability of DTC genomics sector
Where the genomics technology sector has rosy prognostications, the direct-to-consumer personalized genomics market has volatility. Events in the last several months have led to questions of the sector’s viability with upheavals at the three leading companies, 23andme (“Avey Leaves 23andMe to Start Alzheimer's Research Foundation Using DTC Genomics Firm's Platform"), deCODEme (“deCODE close to broke” – Augusty 11, 2009) and Navigenics (“Navigenics Names Jonathan Lord, MD to Serve as President and Chief Executive Officer” April 7, 2009). Absent innovation, DTC genomics companies are a “window business” in the sense that the window for their current offerings may only be open for a short time with the advent of whole human genome sequencing and standardized public multi-SNP condition interpretation tools.

Figure 1. Direct-to-Consumer Genomics Offerings: ongoing price declines (Chart PDF)

As depicted in Figure 1, there are three types of Direct-to-Consumer (DTC) genomics offerings currently available directly to individuals: one-off SNP (single nucleotide polymorphism) tests for specific conditions and paternity tests, multi-SNP risk assessment tests mapping several SNPs to dozens of disease conditions and whole human genome sequencing assessing hundreds of disease risks. The five companies offering multi-SNP risk assessments are: 23andme ($399 for 111 conditions), deCODEme (42 conditions for $985), Navigenics (28 conditions for $999), Gene Essence (84 conditions for $1,195) and Pathway Genomics (77 conditions for $249). 23andme, deCODEme and Navigenics are the most transparent, disclosing the specific SNPs, research references and risk assessment methodologies for their tests, Gene Essence discloses SNPs and Pathway Genomics does not disclose anything. A detailed condition and SNP analysis is here.

Slow DTC genomics adoption
DTC genomics has had slow adoption so far for several reasons, first, there has been very little marketing, few consumers know of the availability and value proposition of DTC genomics services. Second, since automated tools are not yet available, many people are not interested in preventively managing their health, and may still perceive it to be in the responsibility and domain of health care professionals. Third, the conventional but incorrect view is that genetic information is already known (from family history), negative and deterministic. Fourth, as initially pointed out by ExperimentalMan David Ewing Duncan, there are conflicting interpretations from DTC services for the same conditions such as heart attack. This is because the scientific community has little knowledge and agreement yet regarding multi-SNP conditions. DTC companies are looking at different SNPs, assigning different quantitative risk values and employing differing estimates of overall population averages which all contribute to heterogeneous interpretations of risk for the same condition.

Revolutions in biology futures

Biology is continuing its progression from art to information science to engineering problem. As with many technology areas, advances in tools are driving a new era of science, and tools, science and paradigms are all evolving in biology.

DNA Sequencing
The technology for reading DNA, sequencing, is continuing to outpace Moore’s Law. Next-gen high-throughput sequencing leader Pacific Biosciences estimates their 15-minute $1000 genome solution will be on the market in 2013, more than surpassing the Archon X Prize requirements (100 people, 10 days, $10,000 per person).

DNA Synthesizing
The technology for writing DNA, synthesizing, is also extending its capability exponentially. The traditional methods involve laborious manual molecular biology tricks, oligonucleotide synthesis plus ligation, polymerase chain reaction (PCR) and polymerase assembly. These approaches have been supplanted by printing the code directly from a computer or ordering it from any of the 70 worldwide DNA synthesis foundries like Tech Dragon doing a billion dollars of business annually.

Personalized genomics and synthetic biology
The two biggest current revolutions are in personalized genomics and synthetic biology. Therapies are only in the early stages of development but personalized genetic information has the possibility of upstreaming healthcare to tailored medication and preventative interventions. Synthetic biology is using engineering to design and construct biological parts, devices and systems. The field has been developing a foundational library of standard and reliable open-source building block components; to date hundreds have been contributed to the Registry of Standard Biological Parts.

Scientific method yields to combinatorics
In any of the vast areas where biology is now an information science, empiricism and simulation are replacing the traditional scientific method. Instead of hypothesis and trial and error, nearly limitless combinations can be tested and studied for objective understanding of biological phenomena.

A more detailed look at Biology Futures is available here.